Modern Creatinine (Bio)Sensing Challenges of Point-Of-Care Platforms

Biosensors and Bioelectronics 130 (2019) 110–124 Contents lists available at ScienceDirect Biosensors and Bioelectronics journal homepage: www.elsevier.com/locate/bios Modern creatinine (Bio)sensing: Challenges of point-of-care platforms T ⁎ ⁎ Rocío Cánovas, María Cuartero , Gastón A. Crespo Department of Chemistry, School of Engineering Science in Chemistry, Biochemistry and Health, Royal Institute of Technology, KTH, Teknikringen 30, SE-100 44 Stockholm, Sweden ARTICLE INFO ABSTRACT Keywords: The importance of knowing creatinine levels in the human body is related to the possible association with renal, Creatinine muscular and thyroid dysfunction. Thus, the accurate detection of creatinine may indirectly provide information Early diagnosis surrounding those functional processes, therefore contributing to the management of the health status of the Healthcare individual and early diagnosis of acute diseases. The questions at this point are: to what extent is creatinine POC devices information clinically relevant?; and do modern creatinine (bio)sensing strategies fulfil the real needs of Enzymatic biosensors healthcare applications? The present review addresses these questions by means of a deep analysis of the Blood analysis creatinine sensors reported in the literature over the last five years. There is a wide range of techniques for detecting creatinine, most of them based on optical readouts (20 of the 33 papers collected in this review). However, the use of electrochemical techniques (13 of the 33 papers) is recently emerging in alignment with the search for a definitive and trustworthy creatinine detection at the point-of-care level. In this sense, biosensors (7 of the 33 papers) are being established as the most promising alternative over the years. While creatinine levels in the blood seem to provide better information about patient status, none of the reported sensors display adequate selectivity in such a complex matrix. In contrast, the analysis of other types of biological samples (e.g., saliva and urine) seems to be more viable in terms of simplicity, cross-selectivity and (bio)fouling, besides the fact that its extraction does not disturb individual's well-being. Consequently, simple tests may likely be used for the initial check of the individual in routine analysis, and then, more accurate blood detection of creatinine could be necessary to provide a more genuine diagnosis and/or support the corresponding decision-making by the physician. Herein, we provide a critical discussion of the advantages of current methods of (bio)sensing of creatinine, as well as an overview of the drawbacks that impede their definitive point-of-care establishment. 1. Introduction the muscles and other parts of the body, CRE is transported through the bloodstream by the kidneys and excreted in the urine. Accordingly, Creatine is mainly synthesized in the kidneys, liver and pancreas both fluids (blood and urine) deserve clinical attention with respect to (Fig. 1a) before being transported to the tissues and organs, where it is CRE levels (Killard and Smyth, 2000). metabolized to creatinine (Fig. 1b), termed CRE. When adenosine tri- CRE is the second most analysed biomolecule for clinical purposes phosphate is involved in this conversion, creatine per se is a source of after glucose (Joffe et al., 2010). Thus, CRE values outside of typical energy for many biological processes, such as muscle activity ranges is evidence of any health issue associated with renal, muscular (Narayanan and Appleton, 1980). In this context, the creatine to CRE and thyroidal functioning; and levels fairly beyond healthy ones en- cyclization rate is not fully understood despite this knowledge poten- compass very serious diseases, such as chronic kidney disease (CKD), tially assisting in the control of degenerative diseases of the muscles as different types of muscular disorders, cardiovascular problems oreven well as improvement of sport performance (Diamond, 2005). In con- Parkinson's disease, among others. As an example, when CRE levels in trast, it is well-known that CRE levels are fairly constant in the human the serum (i.e., blood) are below 40 µM (Table 1), this indicates an body, mainly depending on the muscle mass of the individual abnormal reduction in muscle mass (Killard and Smyth, 2000). How- (Narayanan and Appleton, 1980; Pundir et al., 2013). For example, the ever, for concentrations greater than 150 µM (Table 1), additional typical reference ranges for serum levels of CRE in healthy patients are analytical tests are required to exclude any risk of CKD. In extreme on the order of 45–90 μM for women and 60–110 μM for men (see cases, values above 500 µM inform of a clear renal impairment that will Table 1; Randviir and Banks, 2013). After subsequent CRE generation in likely involve dialysis treatment or kidney transplantation (Killard and ⁎ Corresponding authors. E-mail addresses: [email protected] (M. Cuartero), [email protected] (G.A. Crespo). https://doi.org/10.1016/j.bios.2019.01.048 Received 18 November 2018; Received in revised form 11 January 2019; Accepted 20 January 2019 Available online 30 January 2019 0956-5663/ © 2019 Elsevier B.V. All rights reserved. R. Cánovas et al. Biosensors and Bioelectronics 130 (2019) 110–124 Fig. 1. General scheme of the metabo- lism of Creatine to CRE. Creatine ori- ginated in different organs is metabolized into CRE in muscles and brain. a) Illustration of the synthetic route of Creatine by the organism together with the main organs in which these processes take place (kidneys, liver and pancreas). AGAT: L-arginine: glycine amidinotransferase and GAMT: S-ade- nosyl-L-methionine: N-guanidinoacetate methyltransferase. Black arrows show where Creatine is required as a source of energy (producing CRE), mainly brain and muscles. b) Creatine metabolization to CRE through hydro- lysis reactions or involving phospho- creatine as an intermediate. CK: Creatine kinase; biosynthesis of creatinine occurs during the reaction. Table 1 serum measurements, as well as the albumin-to-CRE ratio in urine to Ranges of CRE levels found in different matrices from healthy and unhealthy evaluate the state of kidney activity (Cockcroft and Gault, 1976; Junge individuals. et al., 2004; Levey et al., 2015; Omoruyi et al., 2012; Tziakas et al., Sample pH rangea Healthy levels Harmful levels [CRE]a 2015). The early diagnosis of any sort of dysfunction is extremely im- [CRE] portant in the prevention and/or control of CKD because this illness is asymptomatic during the first stages (mild and moderate CKD). Hence, b c c Urine 4.5 – 8 4.4 −18 mM < 3 and > 20 mM when the individual notices any symptom, the disease is likely very Serum / Blood 7.35–7.45 45 – 90 µM (♂) < 40 µM and > 150 µM 60 – 110 µM (♀)d (up to 1 mM)d advanced, and the kidneys are commonly quite damaged. Altogether, Saliva 6.2–7.4 4.4–17.7 µMe 17.7 up to 591 µMe the patient experiences a radical change in their life because CKD Sweat 4–6.8 9.4–18 µMf 60 – 200 µMf treatment involves visiting the hospital every two days for dialysis or, if Tears 6.5–7.5 – – the damage is too severe, that person would need a kidney transplant. ISF 7.2–7.4 g g Importantly, over one million people worldwide are undergoing dia- a (Corrie et al., 2015). lysis treatment. Moreover, the incidence of renal failure has doubled b The range of pH can vary also depending on the different laboratories and, over the last 15 years (Bagalad et al., 2017). Therefore, there is a so- in the case of urine, it can be even wider in case of infection. cietal need for trustable detection of CRE at the point-of-care (POC) c (Li et al., 2015; Ruedas-Rama and Hall, 2010). level not only to allow one to preserve individual well-being and con- d (Killard and Smyth, 2000; Tseng et al., 2018). tribute to a more affordable healthcare system, but also to monitor e (Lloyd et al., 1996; Venkatapathy et al., 2014). patients at advanced stages of CKD, which necessitates more than one f (Al-Tamer et al., 1997; Bass and Dobalian, 1953). The symbol ♂ indicates analysis per day during dialysis treatment (Hannan et al., 2014; males and ♀ in females. Michalec et al., 2016). g Similar levels of CRE can be found in ISF and serum (Ebah, 2012; CRE detection is also crucial in the premature diagnosis of various Kayashima et al., 1992). muscular diseases, such as Duchenne muscular dystrophy (Fitch and Sinton, 1964), myasthenia gravis, acute myocardial infarction Smyth, 2000). Furthermore, persistently elevated levels of CRE may (Radomska et al., 2004b) or guanidinoacetate methyltransferase reveal a high risk of mortality (Levey et al., 2015). Notably, the inter- (GAMT) deficiency (Diamond, 2005), as well as verifying patient status pretation of CRE observations must be always carried out considering before and after surgical interventions (Ho et al., 2012; Prowle et al., the muscle mass of the patient as the same value may be considered 2014; Spahillari et al., 2012; Vart, 2015) or when suffering an accident, normal in a young male with a relatively high muscle mass or may as muscular lesions are somewhat related to higher concentrations of indicate CKD in elderly females (Tseng et al., 2018). CRE in the bloodstream. Besides this, CRE detection is valuable for There are a number of organizations, such as the American verifying dehydration status in individuals, e.g., as a consequence of a Association of Kidney Patients, American Kidney Foundation, National decrease of renal blood flow during or after engaging in strong physical Kidney Foundation in New York and the Nephron Information Center, activity (Baxmann et al., 2008; Mohamadzadeh et al., 2016). In addi- among others1 that define five different stages for kidney function tion, the administration of certain drugs and/or treatments, such as based on the estimated glomerular filtration rate (eGFR), which in turn acetylcholine inhibitors, cyclosporin or chemotherapy, may present is calculated from CRE levels in serum together with other factors, such side-effect damage in the kidneys, and therefore, high levels ofCREare as gender and age.

Load more